Patent GB-710266-A (GB)
Title: New pyrimidine derivatives
Inventor: BOON WILLIAM ROBERT
Filed: 1951-04-06
Abstract: The invention comprises 2-alkoxy-hexahydropyrimidine-4 : 6-dione derivatives and tetrahydropyrimidine-4 : 6-dione derivatives of the respective formul  <FORM:0710266/IV (b)/1> <FORM:0710266/IV (b)/2> wherein R1 stands for an aryl radical, R2 stands for an alkyl radical, R3 stands for hydrogen or for an alkyl radical of not more than 4 carbon atoms and R4 stands for an alkyl radical or an aralkyl radical and hydrates and salts of compounds of formula II.  The salt may be converted to hydrate by adjusting its aqueous solution to pH 6.  The compounds of formula I are prepared by subjecting a 2-thio-barbituric acid of the formula <FORM:0710266/IV (b)/3> or an S-alkyl derivative thereof, to reductive desulphurisation, e.g. by hydrogen-containing finely divided metal catalysts, in the presence of an alcohol of the formula R4OH.  Compounds of the formula I wherein R3 stands for hydrogen, may be produced by reacting in the presence of an alcohol of formula R4OH (a) a malondiamide derivative of the formula R1R2C(CONH2)2 with a formic acid ester; (b) a compound of the formula <FORM:0710266/IV (b)/4> with an alkali metal hydroxide; (c) an ester of a malonic acid derivative of the formula R1R2C(COOH)2 with formamidine.  Compounds of formula I may also be prepared by reacting the compounds of formula II or their salts or hydrates with an alcohol R4OH.  Products of formula II may be prepared by treating compounds of formula I with mineral acids or subliming such compounds in high vacuum.  The products have anti convulsant properties.  They may be used in the process of Specification 710,267.  Raney nickel or cobalt catalysts are suitable.  In examples, 2-ethoxy-5-phenyl 5-ethylhexahydropyrimidine - 4 : 6 - dione is prepared by treating 5-phenyl-5-ethyl-2-thiobarbituric acid with ethanol and (1) Raney nickel (W1); (2) Raney cobalt; (4) Raney nickel (W5); replacing the ethanol of (1) by methanol yields the corresponding 2-methoxy compound.  In further examples: (3) 2-methoxy-5-phenyl-1-methyl-5-ethyl hexahydropyrimidine-4 : 6-dione and the corresponding 1-ethyl compound are prepared by reacting 5-phenyl-1-methyl - 5 - ethyl - 2 - thiobarbituric acid and the corresponding 1-ethyl compound respectively with methanol and Raney cobalt; (5), (7) and (9) 2-methoxy-5-phenyl-5-ethyl-hexahydropyrimidine - 4 : 6 - dione is prepared by reacting (5) a  : a  - phenylethylmalondiamide, sodium, methanol and ethyl formate; (7) diethylphenylethylmalonate, sodium methoxide, methanol, and formamidine hydrochloride; (9) N-formyl - a : a  - phenylethylmalondiamide, methanol and sodium; (6) and (8) 2-ethoxy-5-phenyl - 5 - methylhexahydropyrimidine - 4 : 6 - dione is prepared by (6) reacting a  : a -phenylmethylmalondiamide, ethyl formate, ethanol and sodium; (8) reducing 2-methylthio-5-phenyl-5-ethyl tetrahydropyrimidine-4 : 6-dione with Raney nickel (W1); (10) 5-phenyl-5-ethyletrahydropyrimidine - 4 : 6 - dione monohydrochloride is produced by reacting 2-methoxy - 5 - phenyl - 5 - ethylhexahydropyrimidine-4 : 6-dione in ether with hydrogen chloride gas.  The product reacts with alcohols to give the corresponding 2-alkoxy-5-phenyl-5-ethyl hexahydropyrimidine - 4 : 6 - dione, the 2 - n - propoxy-, 2-iso-propoxy-, 2-n-butyloxy-, 2-sec.-butyloxy-, 2-n-amyloxy-, 2-n-octyloxy- and 2-benzyloxy-derivatives being thus prepared; (11) 5 - phenyl - 5 - ethyltetrahydropyrimidine - 4 : 6-dione monohydrate is prepared by adjusting an aqueous solution of the corresponding monohydrochloride to pH 6 and allowing to stand.  N-Formyl derivatives of the formula <FORM:0710266/IV (b)/5> may be obtained by oxidation of a methylol derivative of the diamide, e.g. with chromic acid.  5 - Phenyl - 1 - methyl - 5 - ethyl - 2 - thiobarbituric acid is prepared by heating phenylethyl malonyl chloride with N-methyl-thiourea. Specification 666,027 also is referred to.